TY - JOUR
T1 - Transplantation of immortalized CD34+ and CD34-adipose-derived stem cells improve cardiac function and mitigate systemic pro-inflammatory responses
AU - Kim, Jong Ho
AU - Choi, Seung Cheol
AU - Park, Chi Yeon
AU - Park, Jae Hyoung
AU - Choi, Ji Hyun
AU - Joo, Hyung Joon
AU - Hong, Soon Jun
AU - Lim, Do Sun
N1 - Publisher Copyright:
© 2016 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell lineages and they are easily obtainable from patients, which makes them a promising candidate for cell therapy. However, a drawback is their limited life span during in vitro culture. Therefore, hTERT-immortalized CD34+ and CD34-mouse ADSC lines (mADSCshTERT) tagged with GFP were established. We evaluated the proliferation capacity, multi-differentiation potential, and secretory profiles of CD34+ and CD34-mADSCshTERT in vitro, as well as their effects on cardiac function and systemic inflammation following transplantation into a rat model of acute myocardial infarction (AMI) to assess whether these cells could be used as a novel cell source for regeneration therapy in the cardiovascular field. CD34+ and CD34-mADSCshTERT demonstrated phenotypic characteristics andmulti-differentiation potentials similar to those of primary mADSCs. CD34+ mADSCshTERT exhibited a higher proliferation ability compared to CD34-mADSCshTERT, whereas CD34-mADSCshTERT showed a higher osteogenic differentiation potential compared to CD34+ mADSCshTERT. Primary mADSCs, CD34+, and CD34-mADSCshTERT primarily secreted EGF, TGF-β1, IGF-1, IGF-2, MCP-1, and HGFR. CD34+ mADSCshTERT had higher secretion of VEGF and SDF-1 compared to CD34-mADSCshTERT. IL-6 secretion was severely reduced in both CD34+ and CD34-mADSCshTERT compared to primary mADSCs. Transplantation of CD34+ and CD34-mADSCshTERT significantly improved the left ventricular ejection fraction and reduced infarct size compared to AMI-induced rats after 28 days. At 28 days after transplantation, engraftment of CD34+ and CD34-mADSCshTERT was confirmed by positive Y chromosome staining, and differentiation of CD34+ and CD34-mADSCshTERT into endothelial cells was found in the infarctedmyocardium. Significant decreases were observed in circulating IL-6 levels in CD34+ and CD34-mADSCshTERT groups compared to the AMI-induced control group. Transplantation of CD34-mADSCshTERT significantly reduced circulating MCP-1 levels compared to the AMI control and CD34+ mADSCshTERT groups. GFP-tagged CD34+ and CD34-mADSCshTERT are valuable resources for cell differentiation studies in vitro as well as for regeneration therapy in vivo.
AB - Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell lineages and they are easily obtainable from patients, which makes them a promising candidate for cell therapy. However, a drawback is their limited life span during in vitro culture. Therefore, hTERT-immortalized CD34+ and CD34-mouse ADSC lines (mADSCshTERT) tagged with GFP were established. We evaluated the proliferation capacity, multi-differentiation potential, and secretory profiles of CD34+ and CD34-mADSCshTERT in vitro, as well as their effects on cardiac function and systemic inflammation following transplantation into a rat model of acute myocardial infarction (AMI) to assess whether these cells could be used as a novel cell source for regeneration therapy in the cardiovascular field. CD34+ and CD34-mADSCshTERT demonstrated phenotypic characteristics andmulti-differentiation potentials similar to those of primary mADSCs. CD34+ mADSCshTERT exhibited a higher proliferation ability compared to CD34-mADSCshTERT, whereas CD34-mADSCshTERT showed a higher osteogenic differentiation potential compared to CD34+ mADSCshTERT. Primary mADSCs, CD34+, and CD34-mADSCshTERT primarily secreted EGF, TGF-β1, IGF-1, IGF-2, MCP-1, and HGFR. CD34+ mADSCshTERT had higher secretion of VEGF and SDF-1 compared to CD34-mADSCshTERT. IL-6 secretion was severely reduced in both CD34+ and CD34-mADSCshTERT compared to primary mADSCs. Transplantation of CD34+ and CD34-mADSCshTERT significantly improved the left ventricular ejection fraction and reduced infarct size compared to AMI-induced rats after 28 days. At 28 days after transplantation, engraftment of CD34+ and CD34-mADSCshTERT was confirmed by positive Y chromosome staining, and differentiation of CD34+ and CD34-mADSCshTERT into endothelial cells was found in the infarctedmyocardium. Significant decreases were observed in circulating IL-6 levels in CD34+ and CD34-mADSCshTERT groups compared to the AMI-induced control group. Transplantation of CD34-mADSCshTERT significantly reduced circulating MCP-1 levels compared to the AMI control and CD34+ mADSCshTERT groups. GFP-tagged CD34+ and CD34-mADSCshTERT are valuable resources for cell differentiation studies in vitro as well as for regeneration therapy in vivo.
UR - http://www.scopus.com/inward/record.url?scp=84959017269&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959017269&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0147853
DO - 10.1371/journal.pone.0147853
M3 - Article
C2 - 26840069
AN - SCOPUS:84959017269
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 2
M1 - e0147853
ER -